Trauma, pathological degeneration, or congenital deformity may result in the need for surgical reconstruction or replacement of bone tissue. Reconstructive surgery is based upon the principle of replacing defective bone tissue with viable, functioning alternatives. In skeletal applications, surgeons have historically used bone grafts. The two main types of bone grafts currently used are autografts and allografts. An autograft is a section of bone taken from the patient's own body, while an allograft is taken from a cadaver. This method of grafting provides the defect site with structural stability and natural osteogenic behavior. However, both types of grafts are limited by certain uncontrollable factors. For autografts, the key limitation is donor site morbidity where the remaining tissue at the harvest site is damaged by removal of the graft. Other considerations include the limited amount of bone available for harvesting, and unpredictable resorption characteristics of the graft. The main limitation of allografts has been the immunologic response to the foreign tissue of the graft. The tissue is often rejected by the body and is subject to the inflammatory response. Allografts are also capable of transmitting disease. Although a thorough screening process eliminates most of the disease carrying tissue, this method is not 100% effective.
Conventional orthopedic implants such as screws, plates, pins and rods serve as loadbearing replacements for damaged bone and are usually composed of a metal or alloy. Although these implants are capable of providing rigid fixation and stabilization of the bone, they cause improper bone remodeling of the implant site due to the large difference in the modulus between bone and metal.
These limitations have initiated the search for a dependable synthetic bone graft substitute. However, in order for an implant to be used as a replacement for bone, it must be capable of both osteointegration and osteoconduction. Osteointegration refers to direct chemical bonding of a biomaterial to the surface of bone without an intervening layer of fibrous tissue. This bonding is referred to as the implant-bone interface. A primary problem with skeletal implants is mobility. Motion of the implant not only limits its function, but also predisposes the implant site to infection and bone resorption. With a strong implant-bone interface, however, mobility is eliminated, thus allowing for proper healing to occur. Osteoconduction refers to the ability of a biomaterial to sustain cell growth and proliferation over its surface while maintaining the cellular phenotype. For osteoblasts, the phenotype includes mineralization, collagen production, and protein synthesis. Normal osteoblast function is particularly important for porous implants that require bone ingrowth for proper strength and adequate surface area for bone bonding.
Calcium phosphate-based materials have been investigated for use as bone replacement materials. Most calcium phosphate biomaterials are polycrystalline ceramics characterized by a high biocompatibility, the ability to undergo osteointegration, and varying degrees of resorbability. Implants made from these materials can be in either a porous or non-porous form. Examples of commercially available calcium phosphate materials include Interpore 200 and Interpore 500. Surgical models using previously developed porous calcium phosphate-based implant materials, however, have shown that porous implants heal more slowly than both autografts and empty defects (Nery et al. J. Periodotol. 1975 46:328; Levin et al. J. Biomed. Mat. Res. 1975 9:183). Studies on tissue ingrowth in non-resorbable implants have also shown that failure of tissue to completely fill the implant can lead to infection (Feenstra, L. and De Groot, K. “Medical use of calcium phosphate ceramics” In Bioceramics of Calcium Phosphate, De Groot, K. Ed., CRC Press, Boca Raton, Fla., 1983, pp 131-141; Feldman, D. and Esteridge, T. Transactions 2nd World Congress Biomaterials Society, 10th Annual Meeting, 1984, p 37).
Implants synthesized from the calcium phosphate-based material, hydroxyapatite (HA), the major mineral constituent of bone, are commercially available in a porous and non-porous form. Synthetic HA implants have excellent biocompatibility. Blocks of dense HA are not useful in reconstructive surgery because they are difficult to shape and do not permit tissue ingrowth. However, in a non-porous, particulate form, HA has been used successfully in both composite (Collagraft) and cement (Hapset) forms (Chow et al. Mater. Res. Soc. Symp. Proc. 1993 179:3-24; Cornell, C. N. Tech. Orthop. 1992 7:55). Due to its fragility and lack of compliance, porous HA have been largely limited to dental and maxillofacial surgery.